Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids
Abstract
C–C bond-forming reactions often require nucleophilic carbon species rarely compatible with aqueous reaction media, thus restricting their appearance in biocatalysis. Here we report the use of nitroalkanes as a structurally versatile class of nucleophilic substrates for C–C bond formation catalyzed by variants of the β-subunit of tryptophan synthase (TrpB). The enzymes accept a wide range of nitroalkanes to form noncanonical amino acids, where the nitro group can serve as a handle for further modification. Using nitroalkane nucleophiles greatly expands the scope of compounds made by TrpB variants and establishes nitroalkanes as a valuable substrate class for biocatalytic C–C bond formation.
Additional Information
© 2019 American Chemical Society. Received: May 20, 2019; Revised: August 14, 2019; Published: August 20, 2019. This work was funded by the Rothenberg Innovation Initiative at Caltech and by a NIH R01 grant (GM125887-01A1). The authors thank Kai Chen for assistance with experiments and Ella Watkins-Dulaney and Kelly Zhang for helpful discussions regarding the manuscript. The authors declare the following competing financial interest(s): The contents of this paper are the subject of a patent application submitted by Caltech, and some authors are entitled to a royalty on revenues arising from that patent.Attached Files
Accepted Version - nihms-1049208.pdf
Supplemental Material - cs9b02089_si_001.pdf
Supplemental Material - cs9b02089_si_002.pdf
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Additional details
- PMCID
- PMC7709965
- Eprint ID
- 98395
- Resolver ID
- CaltechAUTHORS:20190903-130240854
- Rothenberg Innovation Initiative (RI2)
- GM125887-01A1
- NIH
- Created
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2019-09-03Created from EPrint's datestamp field
- Updated
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2022-02-10Created from EPrint's last_modified field